Cryogenic Ablation System and Method

ABSTRACT

A device for treating esophageal target tissue comprises a catheter, a balloon and a refrigerant delivery device. The catheter has a distal portion and a refrigerant delivery lumen. The balloon is mounted to and the refrigerant delivery device is coupled to the distal portion. The refrigerant delivery device comprises a chamber with the refrigerant delivery lumen opening into the chamber, a refrigerant delivery opening fluidly coupled to the balloon interior, and a distribution passageway fluidly coupling the chamber and the refrigerant delivery opening. A refrigerant is deliverable through the refrigerant delivery lumen, into the chamber, through the distribution passageway, through the refrigerant delivery opening and into the balloon interior so to place the balloon into an expanded, cooled state so that the balloon can press against and cool esophageal target tissue. The medical device may include means for sensing a leak in the balloon.

CROSS-REFERENCE TO OTHER APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.12/611,057 filed 2 Nov. 2009, attorney docket WILL 1002-2 (now U.S. Pat.No. 8,382,746); which application claims the benefit of U.S. provisionalpatent application No. 61/116,991, filed 21 Nov. 2008, attorney docketWILL 1002-1.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

None.

BACKGROUND OF THE INVENTION

Throughout the human body there are lumens, such as the esophagus andcolon, which may have components which may become metaplastic orneoplastic. Often, it is desirable to remove or destroy these unwantedtissues. One of these cases where tissue removal and/or ablation aredesirable is Barrett's Esophagus, which is a pre-cancerous condition ofthe esophagus typically often associated with gastric reflux disease(GERD). Although GERD can be medically controlled, Barrett's Esophagusdoes not spontaneous resolve once the GERD has abated. However, it hasbeen shown that if Barrett's Esophagus is ablated, the normal esophaguslining can be restored and therefore lower the risk of developingesophageal cancer.

A variety of techniques have been evaluated for ablation of thiscondition. These techniques include photodynamic therapy, endoscopicresection of the lining of the esophagus, and ablation using a varietyof energy sources such as argon plasma coagulation (APC),radio-frequency (RF) and cryogenic via a direct spray of liquidnitrogen.

BRIEF SUMMARY OF THE INVENTION

An example of a medical device for treating esophageal target tissuecomprises a catheter, a balloon and a refrigerant delivery device. Thecatheter includes proximal and distal portions and a refrigerantdelivery lumen. The catheter also defines a longitudinally extendingcatheter axis. The balloon is mounted to the distal portion. The balloonhas an inner surface defining a balloon interior. The refrigerantdelivery device is coupled to the distal portion. The refrigerantdelivery device comprises a chamber with the refrigerant delivery lumenopening into the chamber, a refrigerant delivery opening fluidly coupledto the balloon interior, and a distribution passageway fluidly couplingin the chamber and the refrigerant delivery opening. A refrigerant isdeliverable through the refrigerant delivery lumen, into the chamber,through the distribution passageway, through the refrigerant deliveryopening and into the balloon interior so to place the balloon into anexpanded, cooled state so that the balloon can press against and coolesophageal target tissue.

In some examples the balloon surrounds at least the portion of therefrigerant delivery device that comprises the refrigerant deliveryopening. In some examples the medical device further comprises means forsensing a leak in the balloon. In some examples the distributionpassageway comprises an annular passageway having a length generallyparallel to and surrounding the catheter axis.

In some examples the refrigerant delivery device comprises a flowdeflector tube, through which the refrigerant delivery opening isformed, and an axially-positionable flow director sleeve at leastpartially surrounding the flow deflector tube. At least one of the (1)refrigerant delivery opening, and (2) the flow director sleeve, has anedge extending at least partially around the catheter axis and along apath having changing rotary and axial positions. The flow deflectorsleeve can be positioned to cover all or part of the refrigerantdelivery opening to affect the delivery of refrigerant into the ballooninterior.

Another example of a medical device for treating esophageal targettissue comprises a catheter, a balloon and a refrigerant deliverydevice. The catheter comprises a main shaft having an open interior,distal portion, an exhaust lumen, and a refrigerant delivery lumen. Thedistal portion has a smaller outside diameter than the main shaft. Theballoon comprises a larger diameter main portion and a smaller diameterstem portion at a proximal end thereof. The smaller diameter stemportion is mounted to the distal portion of the catheter. The ballooncomprises an inner surface defining a balloon interior. The refrigerantdelivery device is coupled to the distal portion. The refrigerantdelivery device comprises a chamber, with the refrigerant delivery lumenopening into the chamber, and a refrigerant delivery opening fluidlycoupled to the chamber and opening into the balloon interior. Arefrigerant is deliverable through the refrigerant delivery lumen, intothe chamber, through the refrigerant delivery opening and into theballoon interior so to place the balloon into an expanded, cooled stateso that the balloon can press against and cool esophageal target tissue.

An example of a method for making a medical device for cryogenicallytreating esophageal target tissue within a target tissue treatmenttemperature range includes the following. A target tissue treatmenttemperature range is determined for cryogenically ablating the targettissue. A balloon material is selected, the balloon material having aglass transition temperature above the target tissue treatmenttemperature range, and having elastic properties above the glasstransition temperature, and being stretch-resistant below the glasstransition temperature. A balloon made of the selected balloon materialis mounted to a distal portion of a catheter assembly. The ballooncomprises an inner surface defining balloon interior. The catheterassembly comprises a catheter comprising a refrigerant delivery lumenfluidly coupled to the balloon interior. A refrigerant can be deliveredthrough the refrigerant delivery lumen and into the balloon interior soto place the balloon into an expanded, cooled state with the temperatureof the balloon lower than the glass transition temperature therebysubstantially preventing any further expansion of the balloon while theballoon cools the esophageal target tissue.

An example of a controlled balloon expansion assembly, for use with aballoon placeable within an open region of a body, the balloon having aninterior and being placeable in inflated and deflated states, includesan exhaust passageway device and a relief valve assembly. The exhaustpassageway device defines an exhaust passageway coupleable to theballoon interior. The relief valve assembly comprises a relief valve, apressurization device and valving. The relief valve comprises a chamberhaving an inlet fluidly coupled to the exhaust passageway, an outletfluidly coupled to an exhaust gas dumping region, and a pressuresensitive sealing element between the inlet and the outlet. The sealingelement is configured to provide a seal between the inlet and the outletaccording to a level of pressure applied to the sealing element. Thevalving selectively fluidly couples the pressurization device to andfluidly isolates the pressurization device from the sealing element andthe exhaust passageway. In some examples the valving comprises a controlvalve placeable in the following states. A first state fluidly couplesthe pressurization device, the pressure sensitive sealing element andthe exhaust passageway to one another. A second state fluidly isolatesthe pressurization device, the pressure sensitive sealing element andthe exhaust passageway from one another. A third state fluidly couplesthe pressurization device to the exhaust passageway. A fourth statefluidly couples the pressurization device to the pressure sensitivesealing element.

Other features, aspects and advantages of the present invention can beseen on review the figures, the detailed description, and the claimswhich follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified overall view of one example of a medical devicemade according to the invention with elements of other examples shown indashed lines;

FIG. 2 is an enlarged, simplified cross-sectional view of the distalportion of a first example of the medical device of FIG. 1;

FIGS. 3 and 4 are simplified illustrations of the effects of highvelocity and low velocity refrigerant flow into the balloon;

FIG. 5 is a view similar to that of a FIG. 2 of another example of themedical device FIG. 1;

FIG. 6 is a view similar to that of FIG. 2 of further example of themedical device of FIG. 1;

FIGS. 6A, 6B and 6C are cross-sectional views taken along correspondinglines of FIG. 6;

FIG. 6D is an enlarged view of a portion of FIG. 6;

FIG. 7 is a view similar to that of FIG. 6D showing alternative shapesof refrigerant discharge jets;

FIGS. 8, 9 and 10 are side views illustrating three differentconfigurations of refrigerant delivery openings;

FIG. 11 shows a typical temperature curve during a procedure in whichthe target tissue is pre-chilled to non-ablative freezing temperaturesfollowed by ablative freezing temperatures;

FIG. 12 illustrates apparatus for selectively coupling two differentrefrigerant cylinders to the refrigerant delivery tube;

FIG. 13 illustrates a refrigerant cylinder with two differentrefrigerants contained within the cylinder and separated by adivider/rupture disk;

FIG. 14 is a simplified view showing how the inner surface of theballoon can be roughened by deforming the balloon wall to help cause therefrigerant to adhere to be balloon inner surface;

FIG. 15 shows the addition of a thin film of absorbent material to theinside surface of the balloon to help cause the refrigerant to collectagainst the inside surface of the balloon;

FIG. 16 illustrates inner and outer balloons defining an interstitialspace within which the refrigerant can be filled;

FIG. 17 shows apparatus to help prevent the balloon from exertingexcessive force against the vessel wall;

FIGS. 17 A, 17 B, 17 C and 17 D illustrate the control valve of FIG. 17in four different positions;

FIG. 17 E illustrates apparatus similar to that of FIG. 5 but withoutthe exhaust sleeve to reduce the restriction to the flow of the exhaustgases;

FIG. 17 F shows another technique for reducing balloon pressure bycreating a lower pressure at the exit port;

FIGS. 18 and 19 are cross-sectional and end views of an example of aballoon in which longitudinally extending filaments are used to create acontainment cage for the balloon to help restrict excessive radialexpansion;

FIGS. 20 and 21 are simplified side and end views showing the use ofnon-compliant strips or wires bonded to the balloon for reinforcement;

FIG. 22 is a view of a balloon reinforced through the use of ahigh-strength adhesive directly to the balloon;

FIGS. 23 and 24 are simplified cross-sectional views of a reinforcedballoon having a variable thickness wall shown in contracted andexpanded states;

FIG. 25 shows structure similar to that of FIG. 6 but also including apressure detection lumen having an opening at its tip to monitor thepressure within the hollow body structure distal of the balloon so topermit detection of a leak;

FIG. 26 shows a structure similar to that of FIG. 25 in which the flowdetection lumen terminates at a cross hole formed at the joint betweenthe distal end of the balloon and support structure so the failure ofthe joint will create a sudden change in pressure within the lumen;

FIGS. 27 and 28 are side cross-sectional and end cross-sectional viewsof a portion of a placement catheter including a thermo resistiveelement placed along the exhaust gas stream to permit detection of aleak by monitoring for a drop in flow rate;

FIG. 29 is a side cross-sectional view of structure similar to that ofFIG. 5 in which the refrigerant delivery nozzle is shaped to sprayrefrigerant over about 180° of the balloon;

FIG. 30 is a cross-sectional view taken along line 30-30 of FIG. 29;

FIG. 31 is a simplified cross-sectional view of structure similar tothat of FIG. 29 in which the refrigerant delivery nozzle extendscompletely around the circumference and is oriented at an angle to theaxis, similar to that shown in FIG. 8, the structure having an axiallypositionable flow director sleeve used to permit selectively changingthe circumferential extent of the refrigerant spray;

FIGS. 31A and 31B are simplified views illustrating how the structure ofFIG. 31 can have the circumferential extent of the refrigerant sprayvaried between 0° and 360° by the axial movement of the flow directorsleeve;

FIGS. 32, 32A and 32B show another configuration in which therefrigerant delivery nozzle is a full circumferential nozzle normal tothe axis of the shaft with the flow director sleeve having an angled cutout so that the position of the flow director sleeve determined how muchof the nozzle is exposed; and

FIG. 32C is an overall view of the flow director sleeve of FIGS. 32, 32Aand 32B.

DETAILED DESCRIPTION OF THE INVENTION

The following description of the invention will typically be withreference to specific structural embodiments and methods. It is to beunderstood that there is no intention to limit the invention to thespecifically disclosed embodiments and methods but that the inventionmay be practiced using other features, elements, methods andembodiments. Preferred embodiments are described to illustrate thepresent invention, not to limit its scope, which is defined by theclaims. Those of ordinary skill in the art will recognize a variety ofequivalent variations on the description that follows.

All of the techniques listed above for ablation of Barrett's Esophagussuffer from ‘usability’ drawbacks. Photodynamic therapy renders thepatient susceptible to sunlight for several months following treatmentand has a high procedural complication rate. Mechanical resection istraining intensive and may not achieve 100% removal of the condition.Ablation techniques such as APC only treat a small area at a time andcontrolling the depth of ablation is difficult. Current RF ablationtechniques require precise sizing of the treatment catheter and requireanother console for the physician to operate. The direct spray of liquidnitrogen can be training intensive and is very operator dependent; thissystem also requires an additional console and a constant supply ofliquid nitrogen.

The present invention addresses many of the limitations of the currenttechnologies. The invention is particularly useful for treatingBarrett's esophagus but may also be useful for treating other esophagealtissues, typically by cryogenic ablation of the atypical tissue.

According to some embodiments of the invention, see FIGS. 1 and 2, themedical device 10 comprises a catheter assembly 12 and a refrigerantsupply 14. The catheter assembly 12 comprises a balloon 16, preferablyan elastomeric material such as polyurethane or silicone, mounted to aplacement catheter or shaft 18. In one embodiment the balloon 16 will becapable of producing an inflated diameter of between 15-45 mm. Inanother embodiment, multiple balloon sizes may be required to cover thedesired range of esophagus sizes; in this embodiment, it is desirable tohave individual balloon diameters that are variable by at least 2 mm.For example, 6 different sizes could be developed to cover the completerange of 15-45 mm in which case each size covers a 5 mm range. Theballoon length may be 10-100 mm. The shaft 18 may comprise a plasticsuch as polyurethane such that the balloon may be appropriately bondedto the shaft; other appropriate, biocompatible materials such as PEBAXand polyethylene may also be used. The shaft 18 will typically be lessthan 8-Fr if it is to be compatible with a conventional diagnosticendoscope, which typically has an accessory channel size of 2.8 mm.However, larger shaft sizes up to, for example, 11-Fr may be used forcatheters designed for conventional therapeutic endoscopes. Shaft 18 mayinclude a refrigerant delivery lumen, not separately illustrated, formedwithin a separate refrigerant delivery tube 22 which may be used fordelivery of the refrigerant. Delivery tube 22 is shown running through,and may be concentric with, the shaft 18 and may have an inner diameterof, for example, 0.004-0.025″ (0.10-0.71 mm). In some embodiments all orpart of delivery tube 22 could also pass along the exterior of shaft 18.This delivery tube 22 may comprise a high-strength plastic material suchas polyimide. Alternatively, delivery tube 22 may comprise a metalhypotube. Typical metals for hypotube include stainless steel andnitinol. In other embodiments, the placement shaft 18 itself will defineat least a portion of the refrigerant delivery lumen.

Medical device 10 also includes a refrigerant delivery device 20 at thedistal end 38 of shaft 18. A fluid saturated liquid/gas refrigerant 24,indicated by arrows 24 in FIG. 2, such as nitrous oxide or ahydrofluorocarbon, is provided from the refrigerant supply 14 through amanifold 26 at the proximal end 28 of the shaft 18, through therefrigerant delivery lumen defined within the delivery tube 22, throughrefrigerant delivery device 20, and into the interior 30 of the balloon16. As shown in FIG. 1, one example of a refrigerant supply 14 ofmedical device 10 comprises a flow control device 32 which may behand-held, coupled to a disposable cylinder 34 of refrigerant. The sizeof the cylinder 34 may be, for example, between 10 to 50 cubiccentimeters in volume. The refrigerant supply 14 may be integral to thecatheter assembly 12 or stand-alone. The refrigerant 24 will typicallybe continuously injected, at room temperature or warmer, through thelumen within the delivery tube 22 and in some embodiments will exit intothe interior 30 of the balloon 16. The refrigerant will then undergo aphase change from liquid to gas, simultaneously expanding the balloonand rapidly drawing energy from the surrounding esophageal tissue andcausing the tissue to be cooled. The gas may then exhaust though shaft18 and exit out of the manifold 26 though an exit port 27. In some otherembodiments, the refrigerant supply may require external heating tomaintain the desired delivery pressure. The balloon 16 will then expanduntil contact with the tissue of the esophagus 36, shown in FIG. 9, hasbeen made.

The placement of the balloon 16 at the target site and expansion of theballoon is preferably monitored by conventional techniques, such asdirect endoscopic visualization. Other endoscopic spectroscopytechniques such as Fluorescence, Raman, or Light Scattering may beuseful for identification of atypical esophageal tissue. In order tolower the risk of injury to the esophagus, the balloon pressure shouldbe minimized such that the effective pressure applied to the esophagusis less than 10-psig. Balloon pressure is primarily dependent on therefrigerant flow rate and can be controlled by manipulating the sizes ofthe interior 46 of shaft 18 and/or the lumen of delivery tube 22.Pressure can also be controlled though a back-pressure regulator 29,shown in dashed lines in FIG. 1, attached to port 27. Techniques forcontrolling expansion of balloon 16 are described below.

Cooling of the esophagus, in particular the atypical esophageal tissue,is typically achieved by evaporation of liquid refrigerant in theballoon 16 which will draw heat away from the esophageal tissue at thetarget site. In order to ablate or otherwise alter the atypical tissue,it is desirable to cool this tissue until it has frozen. Typically,intracellular ice formation is required for substantial necrosis of theatypical tissue. The target temperature to achieve sufficientintracellular ice formation in the atypical esophageal tissue may bebetween −25 and −100° C. As undesirable side effects of the cryoablationtreatment such as esophageal perforation or stricture may occur ifnecrosis occurs deeper than the mucosa, the depth of ablation may becontrolled by regulating the time that the cooling is applied to theesophagus. Based on typical mucosal thickness of 0.5-2 mm, the requiredtime for ablation may be less than 60 seconds.

FIG. 2 is a cross-sectional view of a distal portion of a first exampleof catheter assembly 12 illustrating refrigerant delivery device 20. Thedistal end 38 of shaft 18 has a smaller diameter than the main portion40 of shaft 18. Thus, when the proximal end 42 of balloon 16 is securedto the outer surface of distal end 38 and is in its collapsed state, theoverall diameter of balloon 16 surrounding distal end 38 of shaft 18 canbe reduced compared with mounting the balloon to the larger diametermain portion 40.

Refrigerant delivery device 20 includes a support wire 44 having itsproximal end secured within the interior 46 of shaft 18, typically withan adhesive or a potting compound 48. Support wire 44 passes from thetip 50 of shaft 18 and through the interior 30 of balloon 16. The tip 52of support wire 44 is adhesively or otherwise secured to the distal end54 of balloon 16 through a sleeve 56.

Refrigerant tube 22 passes through potting compound 48 with the tip oftube 22 opening into a chamber 58 defined by distal shaft end 38,potting compound 48 at one end and a tubular guide sleeve 60 at theother end. The central opening through guide sleeve 60 is oversizedrelative to support wire 44 to permit the passage of refrigerant 24 fromchamber 58, through a distribution passageway 59 between support wire 44and guide sleeve 60, and into interior 30 of balloon 16.

In addition to ablation depth control, uniform surface ablation over theentire surface of the target site is also necessary. To achieve this,and assuming the entire outer surface of the expanded balloon 16 is usedto contact the target site, the liquid refrigerant must be uniformlyapplied to the full inner surface 61 of balloon 16. One method of fullradial distribution is shown in FIG. 2. A sleeve like flow deflector 62is secured to support wire 44, typically by an adhesive, a distance 64from tip 50. The gap between flow deflector 62 and tip 50 creates anozzle or jet 65 type of fluid delivery opening through whichrefrigerant 24 flows toward the inner surface of balloon 16. Distance 64is typically about 0.025 mm-0.51 mm (0.001 inch-0.020 inch). This causesa refrigerant 24 to be radially deflected over a 360° angle so that theentire circumferential surface of balloon 16 is cooled by refrigerant24. Refrigerant 24 exits interior 30 of balloon 16 through exhaust holesor ports 66 formed in distal end 38 of shaft 18 and into interior 46 ofshaft 18, which acts as an exhaust lumen. In this example refrigerantdelivery device 20 generally includes potting compound 48, guide sleeve60, flow deflector 62 and support wire 44.

By increasing or reducing the cross-sectional area of the gap betweensupport wire 44 and guide sleeve 60 and by adjusting distance 64, thevelocity of the refrigerant can be increased or decreased as necessaryto propel the refrigerant to reach the inner surface of the balloon.Typically, the gap between support wire 44 and sleeve 60 will be lessthan 0.127 mm (0.005 inches). This feature has significant importance asthe diameter of a balloon 16 increases because refrigerant 24 hasfarther to travel to reach inner surface 61 of the balloon and istherefore increasingly affected by the two primary forces, gravitysuggested by arrow G in FIGS. 3 and 4, and forces associated with themotion of the exhaust gas, suggested by arrows EGF. As shown in FIG. 3,when the velocity of the liquid refrigerant is too low, the refrigeranttends to form a pool 67 of refrigerant 24 on the bottom surface of theballoon 16. Furthermore, the exhaust gas refrigerant 24 tends to push astream of liquid refrigerant 24A towards the exhaust ports 66. However,as shown in FIG. 4, when refrigerant 24 is expelled at a high velocity,the high velocity refrigerant 24 is able to overcome both gravity andthe exhaust gas forces to fully coat the inside surface 61 of theballoon 16 with liquid refrigerant 24B. The shape of the deflectingsurface 63 of deflector 62 can also be adjusted to modify the spraypattern.

FIG. 5 illustrates another embodiment in which the distal end 38 ofshaft 18 is shorter than with the embodiment of FIG. 2. Refrigerantdelivery device includes sleeve like flow deflector 62A and flowdeflector sleeve 62B secured to support wire 44 and are separated toprovide jets 65 therebetween. The distal end of refrigerant deliverytube 22 is secured within the interior of flow deflector sleeve 62B andopens into chamber 58, chamber 58 being defined within flow deflectorsleeve 62B. In this embodiment refrigerant 24 passes directly fromchamber 58 to jets 65. A reduced diameter exhaust sleeve 68 extends fromdistal end 38 and has one or more exhaust holes 66 formed thereinthrough which exhaust gas 124 can flow. In this embodiment, the outsidediameters of flow deflector 62A and flow deflector sleeve 62B can have areduced diameter relative to the inside of the distal end 38 of shaft 18to which proximal end 42 of balloon 16 is secured. This permits theprofile of balloon 16 when in a collapsed or folded state to be reduced.In some examples exhaust sleeve 68 can be eliminated if support wire 44is secured directly to distal end 38 while leaving distal end 38sufficiently open at tip 50 to permit exhaust gas 124 to flow into theinterior 46 of shaft 18.

FIGS. 6 and 7 illustrate a third embodiment in which multiple jets 65are used to provide more uniform axial distribution of refrigerant 24.This is especially helpful for longer balloons. The embodiment of FIG. 6differs from that of FIG. 2 in another manner. A delivery adapter tube70 is fixed within distal end 38 of shaft 18, typically using anadhesive or potting compound 72. The distal end of tube 70 is filledwith a potting compound 71 or other plug structure. Delivery adaptertube 70, potting compound 71, and potting compound 48 surroundingrefrigerant delivery tube 22 define chamber 58. One or more holes 74 areformed in delivery adapter tube 70. Refrigerant 24 passes through holes74 and into distribution passageway 59 defined between delivery adaptertube 70 and flow deflector sleeve 62C. Refrigerant 24 then passesthrough jets 65 into interior 30 of balloon 16. The use of distributionpassageways 59 in the embodiments of FIGS. 2 and 6 between chamber 58and jets 65 helps to ensure proper distribution, typically substantiallyeven distribution, of refrigerant 24 to jets 65. Distributionpassageways 59 thus act as simple manifolds for the proper distributionof refrigerant 24.

The embodiment of FIG. 6 uses flow deflector 62A and flow deflectorsleeve 62C which are separate elements from distal end 38 of shaft 18.This enables jets 65 to be full, 360° delivery jets. While flowdeflector sleeve 62C may be affixed to adapter tube 70 at, for example,three circumferentially spaced positions, in some embodiments it may befree-floating on the adapter tube 70 so that the pressure of refrigerant24 causes flow deflector sleeve 62C to become centered on tube 70. Otherexamples may have flow deflector 62A and flow deflector sleeve 62C beextensions of the distal end 38 of shaft 18.

In another embodiment, flow deflector sleeve 62C can be designed torevolve around chamber 58. This feature can be used to improve theuniformity of the refrigerant spray. In another embodiment, a focalspray of refrigerant will be rotated around the inside surface of theballoon. This has the effect to raise the average temperature of thetherapy, compared to a continuous spray. This can be used to make arelatively ‘colder’ refrigerant such as nitrous oxide, which evaporatesat about minus 90° C. at atmospheric pressure, mimic the effect of a‘warmer’ refrigerant such as R-410a, which evaporates at about minus 50°C. at atmospheric pressure.

Full, 360° distribution of refrigerant 24 may not require that the gapsdefining the refrigerant delivery openings, that is jets 65, becontinuous. Also, the gaps defining jets 65 need not have a constantlongitudinal or axial position. For example, FIG. 7 illustrates avariable width over the length of jets 65 and FIGS. 8-10 illustratethree different circumferential shapes of jets 65 that can be used toprovide a degree of longitudinal spray to refrigerant 24. In particular,the refrigerant delivery opening 65 of FIG. 8 defines an oval pathextending along the axis of tube 70 at an acute angle to the axis. InFIG. 9 the refrigerant delivery opening 65 defines a path having aseries of generally straight segments extending along the axis atdifferent acute angles to the axis with adjacent segments extending inopposite axial directions. FIG. 10 shows an example in which therefrigerant delivery opening 65 defines a path extending along the axis,the path having at least one and preferably at least two generallyS-shaped curved segments.

Additional shapes and arrangements for the gaps defining jets 65, suchas a series of circular holes and/or oblong slots, could also be used.Although a number of examples are described herein, the invention is notlimited to the examples shown.

The examples so far discussed have all provided coverage oversubstantially 360°. By making the gaps defining jets 65 be more limitedin scope, ablation over only a portion, such as about half or about onequarter, of the circumference can be achieved. In this case, it may bedesirable to ablate only these portions of the esophagus. One embodimentof the invention for doing so is illustrated in FIGS. 29 and 30. In thisdevice, the refrigerant flow is directed through a refrigerant deliverynozzle 128 into some portion of the circumference of balloon 16. Aspreviously disclosed, significant heat transfer is only possible wherethe liquid refrigerant is evaporating on inner surface 61 of balloon 16.For example, the system could be designed to treat approximately ½ ofthe circumference, by designing the system to only spray refrigerant onapproximately ½ of the circumference of the inside of the balloon asshown in FIGS. 29 and 30. In the case that full circumference treatmentwas desired, the user could perform a treatment and then rotate thecatheter 180°. Alternatively, the user could choose to treat theuntreated portion of the esophagus at some later date, e.g. 30 dayslater, as this may reduce the possible of undesirable complications,such as esophageal stricture. Refrigerant delivery nozzles 128 can beformed having greater or lesser spans of coverage. Also, refrigerantdelivery nozzles 128 may not be continuous but could be two or morenozzle segments. Further, two or more refrigerant delivery nozzles 128can be located at axially spaced apart positions.

In other embodiments, the device is able to selectively treat a variablecircumference. In one configuration, see FIGS. 31-31B, refrigerantdelivery nozzle 128 is a full circumference nozzle but is formed at anangle to the axis of shaft 18 as shown in FIGS. 8 and 31A. The axialposition of a flow director sleeve 130 determines how much of nozzle 128is exposed. In FIG. 31A entire nozzle 128 is exposed while in FIG. 31Babout half of the nozzle is covered by sleeve 130. This permits the userto adjust the extent of the spray among a range of spray angles from360° to essentially no spray. The flow director sleeve 130 can beconnected to a wire which passes though shaft 18 to allow the user tocontrol the axial position. In another configuration, see FIGS. 32-32C,refrigerant delivery nozzle 128 is a full circumference nozzle normal tothe axis of shaft 18. Flow director sleeve 130A has a cutout region 132leaving a stabilizing ring 134 at its distal end connected to theremainder of sleeve 132 at a junction 136. Cutout region 132 alsodefines a distally facing edge 138 arranged at an angle, such as 45°, toits axis. The axial position of a flow director sleeve 132 determineshow much of nozzle 128 is exposed. In FIGS. 32 and 32A substantially theentire nozzle 128 is exposed so to permit delivering a refrigerant insubstantially a full 360° pattern. In FIG. 32B, most of nozzle 128 iscovered by sleeve 130A thereby delivering refrigerant over about 1/8 ofthe circumference.

Typically, increasing treatment times will also improve the uniformityof the ablation. Long treatment times allow for more uniform surfacecooling due to thermal conductivity of the lumen being treated;furthermore, longer treatment times are more likely to mitigate thesomewhat random nature of refrigerant spray within the balloon (due tomanufacturing variances, uncertainty associated with two phaserefrigerant flow, etc). On the other hand, increasing treatment timesgenerally results in a deeper effect than may be desired. Therefore itis desirable to protect the deeper tissues from the thermal insult whenincreasing the treatment times. For example, one way to increasetreatment time is to pre-chill or pre-freeze the extracellular water inthe target tissue to a non-lethal temperature (typically ˜−10 to −2° C.)and then immediately drop the temperature to induce intracellular iceformation in the target tissue (˜<−15° C.). FIG. 11 shows a typicaltemperature curve for this pre-chilling treatment. Solid line 85 is theballoon temperature at the point of most rapid cooling and dashed line87 shows the slowest cooling rate of the balloon. During the first phaseof treatment, the entire target tissue is cooled to non-ablativefreezing temperatures. The duration of this first phase is such that thetissue in contact with the balloon area of slowest cooling freezes. Thisduration will not typically be ‘actively’ controlled, but ratherexperimentally determined by testing a wide range of catheters andstatistically determining the ideal duration. During the second phase oftreatment the balloon temperature is dropped rapidly to induce necrosisin the target tissue. The tissue can be cooled extremely rapidly duringthis phase as the energy requirements to reach necrosis inducingtemperatures is much lower as much of the tissue is already frozen;furthermore, the specific heat capacity (C_(p)) of the frozen tissue islower than the C_(p) of normal tissue. Additionally, the tissue can bemore uniformly cooled as the thermal conductivity of the frozen tissueis much higher than that of normal tissue. The third phase typicallyconsists of the natural warming of the tissue.

A variety of means are available to induce this type of temperaturegradient. It may be desirable to develop multiple temperature profilealgorithms to treat to differing target treatment depths.

In one embodiment, the balloon pressure could be decreased at the timethat the temperature drop was required. As the evaporation temperatureof the refrigerant is directly related to the balloon temperature, thispressure drop will result in a temperature drop within the balloon.Ideally, the chosen refrigerant will have a fairly large temperaturechange relative to pressure as it is desirable to operate the balloon atpressures less than 1 atmosphere unless additional balloon diameterlimiting features have been employed.

In another embodiment, multiple refrigerants can be used to create thevariable temperature effect. In the example of FIG. 12, two refrigerantcylinders 34A and 34B are selectively connected to refrigerant deliverytube by valves 35A and 35B. During operating, refrigerant A (typicallyR134a, R422b, or similar) in cylinder 34A would first used for thewarmer extracellular cooling/freezing temperature. Refrigerant B(typically R404, R410a, or nitrous oxide) in cylinder 34B would then beused to induce intracellular ice formation to achieve the desired damageto the tissue.

In other embodiments, the two refrigerants could be contained in asingle cylinder. One method for accomplishing this is shown in FIG. 13.In this design, Refrigerant B, the lower temperature refrigerant, isplaced into cylinder 34C followed by a divider/rupture disc 82. Thedivider/rupture disc 82 can be press-fit or the cylinder can be swagedto create a tight seal. The cylinder would then be kept at asufficiently low temperature that prevents failure of the rupture disc.Refrigerant A, the higher temperature refrigerant, is then placed intocylinder 34C and an end cap 84 with a penetrable seal 86 is press-fit orswaged into the end of the cylinder. As the pressure of Refrigerant A isnow acting on the opposite side of the rupture disk 82, the disk willnot fail. During operation, seal 86 of cylinder 34C is punctured and theinitial cooling is conducted with Refrigerant A. Once Refrigerant A hasbeen fully consumed, the pressure in that portion of the chamber willfall, resulting in failure of rupture disk 82. Once rupture disk 82 hasfailed, Refrigerant B will be delivered to the balloon 16, completingthe treatment.

It is also possible that the two refrigerants are insoluble in eachother and the liquid phase of Refrigerant A is of higher density thanthe liquid phase of Refrigerant B. In this event, the two refrigerantscould be placed in a cylinder without a divider/rupture disk 82.

Another technique to improve balloon surface temperature distribution isthe addition of a heat transfer medium to the refrigerant. Although thishas the net effect of reducing the absolute cooling power of the system,it functionally increases the heat transfer coefficient of the balloon.For example, a material such as silicone or mineral oil can be dissolvedinto the refrigerant at the time of bottling. Typically, the percentage(by volume) of oil would be 1-10%. Under normal operation (i.e. no addedheat transfer medium), refrigerant exits the delivery side into theballoon at a temperature approximately equal to the delivery cylindertemperature. As the refrigerant exits the delivery side, the pressure ofthe refrigerant drops rapidly causing some evaporation and super-coolingof the remaining liquid refrigerant. The super-cooled liquid thenstrikes the balloon wall and evaporates, creating a gas barrier betweenthe liquid refrigerant and the balloon wall. Therefore, by adding anon-volatile element to the liquid refrigerant, improved heat transferwill occur as the liquid refrigerant will also cool the heat transfermedium which will tend to adhere to the balloon surface.

Additionally, the refrigerant distribution may be aided by reducing theeffect of refrigerant surface tension, which causes the refrigerant toflow as a sheet on the inside of the balloon. The surface tension of therefrigerant could be reduced by the addition of a surfactant such assodium lauryl sulfate or polyethylene glycol to the refrigerant. In somecases the surfactant can be applied to the inner surface of the balloon.

Another technique to mitigate the effect of surface tension is to alterthe inner surface 61 of balloon 16 so that it is not a uniform surface.One technique, illustrated in FIG. 14, would be simply to roughen innerballoon surface 61. One way of doing so would be to deform the entirewall thickness as shown in FIG. 14. Roughening inner surface 61 could beaccomplished by chemically or otherwise treating only inner surface 61of balloon 16. Another way would be the addition of a thin film ofabsorbent material 88 to inside balloon surface 61 as shown in FIG. 15.That is, absorbent material 88 would tend to absorb the refrigerant tohelp keep the refrigerant adjacent to the inner balloon surface.

In another embodiment, see FIG. 16, the refrigerant could be injectedinto an interstitial space 90 created by using inner and outer balloons16A and 16B as shown in FIG. 16. As the volume of this space 90 isrelatively small, the entire volume could be safely filled with liquidrefrigerant, thereby creating a uniform surface temperature. Theinterior 89 of inner balloon 16A would typically be filled with a fluidsuch as air, which has low specific heat capacity and thermalconductivity.

It may be desirable to control the expansion of the balloon so as toprevent excessive force being applied to the esophagus while taking thenative shape of the esophagus applying consistent ablation along thetarget treatment site. In such cases, it may be useful to exploit thepressure-diameter relationship of elastic balloons. In one embodiment,as shown in FIG. 17, a controlled balloon expansion assembly 91comprises a relief valve assembly 93 and shaft 18. Shaft 18 is fluidlycoupled to interior 30 of balloon 16. Relief valve assembly 93 includesa chamber 92 fluidly coupled to interior 46 of shaft 18. Relief valveassembly 93 also includes a syringe 96, or other user-controlledpressurization device, and valving, such as a control valve 98. Withinchamber 92 is a bladder 94 which is in fluid communication with syringe96. Control valve 98 controls flow from syringe 96 to both bladder 94and shaft 18. A refrigerant delivery tube 22 is disposed within shaft18. Refrigerant delivery tube 22 could be routed to balloon 16separately from shaft 18; for example, the distal end of tube 22 couldbe passed into the end of balloon 16 opposite to where shaft 18 entersthe balloon. Syringe 96 is typically filled with a gas such as air.

The control valve 98 is placed in position 1 of FIGS. 17 and 17A andbladder 94 and balloon 16 are pressurized with gas from syringe 96. Aflow restriction device 100 is placed between control valve 98 and shaft18 so that bladder 94 inflates at a faster rate than balloon 16 toprevent the gas from syringe 96 from escaping through an opening 101 inchamber 92 and into the ambient environment, or other exhaust gasdumping region. Under direct visualization, balloon 16 is inflated tothe desired diameter. Once the desired diameter is achieved, controlvalve 98 is placed into position 2 of FIG. 17B so that no fluid flowsthrough valve 98. Refrigerant flow through delivery tube 22 isinitiated, passes into balloon 16 and then out of the balloon backthrough interior 46 of shaft 18 and into chamber 92. Once the pressurein chamber 92 exceeds the pressure in bladder 94, the bladder issufficiently deformed allowing the exhaust refrigerant gas 124 to passthe bladder and exit to atmosphere through opening 101 in chamber 92thereby regulating balloon pressure (and therefore balloon diameter) toa pressure slightly greater than the pressure in the bladder. Oncetreatment is complete, the control valve is placed in position 3 of FIG.17C to allow evacuation of and thus deflation of balloon 16 with exhaustgas 124 passing into syringe 96. As bladder 94 is still inflated, theballoon can hold vacuum and thus be completely collapsed through the useof syringe 96; this helps to facilitate removal of the balloon from theendoscope (not shown) or other placement device. The use of syringe 96instead of some other type of pressurization device provides theadvantage of using one device to both pressurized bladder 94 and tocreate a suction force to help collapse balloon 16. If another treatmentis desired, the control valve can be placed into position 1 of FIG. 17Aand the process can begin again. If desired, bladder 94 can beindependently inflated and deflated by placing valve 98 into position 4of FIG. 17D.

In some examples valve 98 can be replaced by two valves, each coupled tosyringe 96 with one valve coupled to bladder 94 and the other valvecoupled to interior 46 of shaft 18, typically through flow restrictiondevice 100. In some examples bladder 94 can be replaced by a differenttype of pressure sensitive sealing element. For example, bladder 94could be replaced by a piston and cylinder arrangement fluidly coupledto control valve 98 and used to operate a flapper valve within chamber92; when a sufficient pressure within interior 46 of shaft 18 wasachieved, the pressure would cause the flapper valve to opensufficiently permit the passage of the exhaust valve on 24 past theflapper valve and out through opening 101.

In embodiments with highly compliant balloons, the balloon pressure mayneed to be much lower than 10-psig. In these cases, maximizing the sizeof the exhaust lumen is necessary. Typically, the smallest hydraulicdiameter is in the area of the proximal end 42 of balloon 16. As shownin FIG. 17E, this diameter can be maximized by having only refrigerantdelivery tube 22 pass through this area. In order to achieve thelongitudinal stiffness required for passage thru the endoscope,refrigerant delivery tube 22 would typically be constructed from astainless steel hypotube. Alternatively, the delivery tube could be aplastic such as polyimide, and a metal support wire could pass throughthe length of the catheter. Rigid refrigerant delivery tube 22 alsoprovides longitudinal stiffness for balloon 16.

In other cases, the balloon pressure can be lowered by connecting theproximal end 28 of shaft 18 to a suction source in the procedure room.Alternatively, the vacuum could be created by the integrating a Venturivacuum generator 138 into the device as shown in FIG. 17F. Generator 138includes a nozzle 140 connected to refrigerant delivery tube 22.High-pressure refrigerant flows from nozzle 140 through a constrictingexit port 27 a. This creates a lower pressure at exit port 27 a helpingto pull exhaust gas stream 124 through shaft 18 and out of the shaftthrough exit port 27 a.

Additionally, exploiting the glass transition temperature (Tg) of theballoon material is also useful to preventing over-dilatation of theesophagus. For example, the balloon is statically inflated to thedesired size and the refrigerant flow is then initiated. Due to the lowthermal mass of the balloon, virtually instantaneous cooling is achievedand due to the glass transition temperature of the material being higherthan the refrigerant evaporative temperature, the modulus of the balloonincreases dramatically causing the balloon to be stretch-resistant. As aresult, further expansion of the balloon is prevented. Therefore, it isdesirable to select a polymer that has low modulus so that it isstretchy at normal body temperatures (˜37° C.), and high modulus so thatit is stretch-resistant at the target therapeutic ablation temperature,sometimes called the target tissue treatment temperature range(typically within the range of −15 to −90° C.). Many materials areavailable to meet this objective and can be blended to achieve the idealglass transition temperature. For example, polyurethane has a Tg in therange of −10 to −50° C. commonly depending on the hardness (durometerrating) and a blend could be developed to be compatible with HFC typerefrigerants. Other possible materials include low durometer PEBAX(Tg˜−60° C.), low durometer polyethylene (˜−100° C.), and silicone(˜−130° C.). For example, a suitable target tissue treatment temperaturerange for a particular procedure may be −30 to −60° C. so that thematerial having a glass transition temperature of −50° C. would likelybe a suitable choice.

As there are potential failure modes that could cause patient injury, itmay be necessary to mitigate these risks in some fashion. One cause ofconcern is leaks. As the procedure is done under direct visualization,balloon rupture is likely to be quite easily detected. However, a leakthat occurs distally of the inflated balloon could cause inflation anddilatation of the esophagus and stomach, possibly resulting inperforation before the leak is discovered. One cause of this type ofleak would be a failure of the distal balloon joint at the distal end 54of balloon 16. As a result, prevention and mitigation of this failuremode would be advantageous.

Thermally bonding the balloon 16 to the support structure, such assleeve 56, may be preferred as this method typically results in thehighest strength and is therefore the less likely to fail compared witha method such bonding with adhesive. Also, reinforcing the joint with anon-compliant material such as polyimide or PET can also significantlyreduce joint failure.

Additionally, reducing compliance (that is, expansion) in thelongitudinal direction will also reduce the stress on the joint. One wayto do so is by attaching high tensile strength filaments or strips 102to balloon 16 as shown in FIGS. 18 and 19. Doing so creates acontainment cage is created by the use of high tenacity polymer yarnssuch as Spectra or Zylon. The yarns can be mechanically attached to theballoon stem reinforcing bands 104. Typically 3-8 yarns are required.

In another embodiment the balloon can be reinforced by attachingnon-compliant strips or wires 106 to the balloon as shown in FIGS. 20and 21. Preferably the strips would be constructed from a high strengththin film polymer such as PET or polyimide. The strips could be attachedwith a high strength adhesive 108 such as epoxy.

Alternately, as shown in FIG. 22, balloon 16 could be reinforced with anapplication of a high strength adhesive 110 as shown in FIG. 22. Theadhesive could be applied in any combination of longitudinal andcircumferential directions to achieve the desired reinforcement.

In another embodiment, see FIGS. 23 and 24, balloon 16 could be blownsuch that the wall had thicker portions 112 as shown in FIGS. 23 and 24.The location and orientation of the thicker portions can be adjustedaccording to how the expansion of balloon 16 is to be restricted. Forexample, thicker portions 112 can be formed as longitudinally extendingportions, circumferentially extending portions, spirally extendingportions, or portions extending in some other manner. One method ofmanufacture for longitudinally extending portions is to extrude the basetubing for the balloon as shown in FIG. 23 and then blow the balloon ina mold. If spirally extending portions are desired, the base balloontubing can be twisted as it is drawn off of the extruder. Alternatively,the balloons could be manufactured from several components. For example,the longitudinal stiffening elements could be extruded independently ofthe base balloon tubing and then thermally bonded during the balloonblowing process.

It is also possible to reduce the longitudinal stress by attachingballoon 16 to shaft 18 so that distance between the ends 42, 54 of theballoon is shorter than the actual length of the balloon.

Additionally, detection of a joint failure, either separately or inaddition to automatic cessation of the refrigerant flow as isaccomplished with the example of FIG. 17, is beneficial. One way todetect a leak is to measure pressure distal to the balloon. In oneembodiment, as shown in FIG. 25, a pressure detection lumen 116 runs theentire length of the catheter assembly 12 and is open at its distal tip118. The proximal end is tightly sealed and in fluid communication witha pressure sensing device, not shown, such as a pressure transducer. Toeffectively mitigate damage to the esophagus and stomach, detectingpressure changes of less than 1-psig than would necessary. Furthermore,due to the low threshold detection pressure, a filtering algorithm maybe required to reduce false positives due to esophageal motility andeructation. Alternatively, the pressure in lumen 116 could be connectedto a pneumatic actuator to directly terminate the refrigerant flow. Inanother embodiment, shown in FIG. 26, flow detection lumen 116terminates under distal end 54 of balloon 16 at a cross-hole 120 formedthrough tube 70. In the event that the bond between balloon 16 and tube70 fails so that balloon 16 separates from tube 70, gas is deliveredinto cross-hole 120 and through lumen 116. The sudden change in pressurewithin lumen 116 should be readily detectable.

Another technique to detect a leak is to measure flow of the exhaust gasand terminate the flow of refrigerant in the event of a sudden drop inflow. One method of flow detection is shown in FIGS. 27 and 28. In thisdesign, a low resistance (<1000 ohms, typically ˜100 ohms)thermoresistive element 122 is placed into the exhaust gas stream 124.The thermoresitive element 122 is typically placed in series with aresistor in a typical voltage divider circuit, not shown. Oncerefrigerant flow is initiated, voltage is applied to the circuit (<12VDC, typically 5 VDC) which causes the thermoresitive element 122 toheat. The exhaust gas stream 124 flowing past thermoresitive element 122removes heat from element 122 at some rate proportional to the flowrate. The temperature of element 122 can be determined by measuring thevoltage drop across the element. During use, a rise in the temperatureof element 122 would indicate a drop in the flow rate and thus apotential leak.

If greater accuracy is required, a temperature sensing element 126 couldbe added to the circuit to reduce false-positives due to variations inexhaust gas temperature. Other methods of flow measurement such asmeasuring the pressure drop across some fixed length of the exhaust gasstream 124 could also be utilized.

The above descriptions may have used terms such as above, below, top,bottom, over, under, et cetera. These terms may be used in thedescription and claims to aid understanding of the invention and notused in a limiting sense.

While the present invention is disclosed by reference to the preferredembodiments and examples detailed above, it is to be understood thatthese examples are intended in an illustrative rather than in a limitingsense. It is contemplated that modifications and combinations will occurto those skilled in the art, which modifications and combinations willbe within the spirit of the invention and the scope of the followingclaims.

Any and all patents, patent applications and printed publicationsreferred to above are incorporated by reference.

What is claimed is:
 1. A method for making a medical device forcryogenically treating esophageal target tissue within a target tissuetreatment temperature range, the method comprising: determining a targettissue treatment temperature range for cryogenically ablating the targettissue; selecting a balloon material having a glass transitiontemperature above the target tissue treatment temperature range, theballoon material having elastic properties above the glass transitiontemperature and being stretch-resistant below the glass transitiontemperature; and mounting a balloon made of the selected balloonmaterial to a distal portion of a catheter assembly, the ballooncomprising an inner surface defining balloon interior, the catheterassembly comprising a catheter comprising a refrigerant delivery lumenfluidly coupled to the balloon interior; whereby a refrigerant can bedelivered through the refrigerant delivery lumen and into the ballooninterior so to place the balloon into an expanded, cooled state with thetemperature of the balloon lower than the glass transition temperaturethereby substantially preventing any further expansion of the balloonwhile the balloon cools the esophageal target tissue.
 2. A controlledballoon expansion assembly, for use with a balloon placeable within anopen region of a body, the balloon having an interior and beingplaceable in inflated and deflated states, the assembly comprising: anexhaust passageway device defining an exhaust passageway coupleable to aballoon interior; and a relief valve assembly comprising: a relief valvecomprising a chamber having an inlet fluidly coupled to the exhaustpassageway, an outlet fluidly coupled to an exhaust gas dumping region,and a pressure sensitive sealing element between the inlet and theoutlet, the sealing element configured to provide a seal between theinlet and the outlet according to a level of pressure applied to thesealing element; a pressurization device; and valving selectivelyfluidly coupling the pressurization device to and fluidly isolating thepressurization device from the sealing element and the exhaustpassageway.
 3. The assembly according to claim 2, wherein the valvingcomprises a control valve placeable in the following states: a firststate fluidly coupling the pressurization device, the pressure sensitivesealing element and the exhaust passageway to one another; a secondstate fluidly isolating the pressurization device, the pressuresensitive sealing element and the exhaust passageway from one another; athird state fluidly coupling the pressurization device to the exhaustpassageway; and a fourth state fluidly coupling the pressurizationdevice to the pressure sensitive sealing element.
 4. The assemblyaccording to claim 2, wherein the pressure sensitive sealing elementcomprises an inflatable bladder.
 5. The assembly according to claim 4,wherein the release valve assembly comprises a flow restriction devicefluidly positioned between the valving and the exhaust passageway,whereby when the pressurization device is fluidly coupled to both thepressure sensitive sealing element and the exhaust passageway, theinflatable bladder is inflated at a faster rate than the balloon.